ALTERATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR EXPRESSION IN A PIGLET MODEL OF NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY

01/29/2020

Viktória Kovács¹, Gábor Remzső¹, János Németh¹, Viktória Varga¹, Valéria Tóth-Szűki¹, Ferenc Domoki¹

¹ University of Szeged Faculty of Medicine Department of Physiology

Hypoxic-ischemic encephalopathy (HIE) is elicited by perinatal asphyxia (PA) that can result in adverse neurologic outcomes or death. Currently therapeutic hypothermia (HT) is the only effective neuroprotective therapy in HIE management. Brain-derived neurotrophic factor (BDNF) is a highly expressed member of the neurotrophic factor family in the developing brain.. The purpose of this study was to assess the effect of PA or PA followed by HT on the mRNA levels of BDNF, apoptosis-inducing factor (AIF), and caspase-3 in neonatal piglets. Anesthetized, ventilated piglets were aseptically instrumented and divided into 4 experimental groups: untreated naïve controls, normoxic time controls, animals undergoing 20 min PA and PA+HT. PA was induced by ventilation with a gas mixture containing 4% O2 and 20% CO2 for 20 min followed by reventilation with air. HT (Trectal=33.5°C) was initiated at 2h of reventilation, while rewarming started at 36th hour of survival. At 48 hours after PA, the brains were processed for qRT-PCR. The relative expression of BNDF mRNA showed a significantly lower expression in all examined regions for the PA group and increased expression in the PA+HT group compared to the untreated naïve group. For caspase-3 and AIF no significant expression changes were detected. In conclusion, the modulation of BDNF expression may play a role in the mechanism of HT‑induced neuroprotection in HIE. This work was supported by the Hungarian Science Research Fund OTKA-PD128464, Hungarian Brain Research Program (2.0 1.3 2017 1,2.1 NKP 2017 00002), the EU-funded Hungarian grant EFOP-3.6.1-16-2016-00014 and the GINOP 2.3.2. 15 2016 00034.